The ability of cells to generate and respond to mechanical stimuli is poorly understood. Previous studies have shown that mechanical forces play an important role in cellular functions as varied as gene expression, cell growth and proliferation, cell motility, and wound healing. The importance of proper mechanical signal processing is recognized best in cells that have lost this ability, as with metastatic cancer cells. However, the exact magnitude and pattern of forces, as well as the role of cellular components believed to mediate this function, such as the actin cytoskeleton and cell substrate adhesion molecules, are ill defined. In this proposal, we will investigate the mechanical forces exerted by cells at the cell substratum interface during cell migration. In addition, we will investigate how mechanical forces and mechanical signaling are altered in transformed cultured cells known for their metastatic ability. Using a technique developed in our lab for the detection of mechanical forces and mechanical responses, we will investigate the temporal and spatial distribution of mechanical forces during the migration of normal and transformed cells. We will determine the relationship between mechanical forces and the speed/direction of cell migration, and study the responses of cells to manipulations in substrate adhesion or mechanical interactions. We will also identify any mechanical response that occurs during cell-cell contact of normal and transformed cells. These studies will contribute to the understanding of how mechanical forces promote cell migration and how these forces mediate cell-cell signaling required for contact inhibition of migration.